Genomic analyses of the tumor suppressor protein ING2 in response to cellular stress

In humans and other eukaryotes, genomic DNA is packaged into a polymer called chromatin. Regulation of chromatin architecture plays fundamental roles in diverse cellular processes, and alteration of chromatin homeostasis is implicated in tumorigenesis as well as the pathogenesis of several human diseases. ING2 is a member of a protein complex that modifies chromatin structure, but the molecular basis for ING2-mediated tumor suppression is unclear.  We postulated that ING2 regulates chromatin to modulate a gene expression profile capable of limiting cell growth. To test this hypothesis, we performed chromatin immunoprecipitation coupled with DNA microarrays (ChIP-chip) as well as gene expression microarrays under conditions of genotoxic stress.  We find that ING2 directly regulates expression of genes that control cellular proliferation and chromosome dynamics.  Our data thus support a model in which ING2 functions as a tumor suppressor by regulating gene expression to counter the development of cancerous cells.